Project Summary/Abstract Lung disease annually kills more than 3 million people worldwide and 400,000 Americans (1 out of 6 deaths). More than 235 million people worldwide and 35 million Americans are suffering from chronic lung disease. Over 200,000 American people are suffering from ARDS (adult respiratory distress syndrome) with its mortality rate of 25 - 40%. The traditional respiratory support for ARDS is mechanical ventilation to compensate pulmonary deficiency and to support respiratory function. However, high airway pressure, high oxygen concentration and over-distention can cause many complications, possibly resulting in multi-organ failure. The medical support for the chronic disease can be oxygen therapy and pulmonary vasodilators but the long-term treatment is ultimately lung transplantation. Artificial lung technologies, which are most commonly used for cardiopulmonary bypass during open-heart surgery, have been developed and modified in order to provide respiratory support with the acute as well as chronic lung disease patients. However, the current clinical use of portable artificial lung is very limited to only extracorporeal membrane oxygenation (ECMO) in ICU, only supporting the respiratory needs of patients at rest. Truly portable or long-term (> days) support systems are not available with current technologies due to low gas exchange performance and biocompatibility issues. A crucially important element in artificial lung is the intervened membrane where gas (O2 and CO2) exchange occurs between gas and blood streams. The exchange mechanism is extremely slow diffusion across the streams and membrane. This proposal aims to attack the fundamental mechanism in gas exchange (diffusion) by using an innovative concept of active membrane (AM). The AM generates strong cross-streams, normal to the membrane surface, thus agitates the laminar blood stream, and eventually make a quantum leap in gas exchange. The cross-streams directly carry mass (O2-/CO2-dissolved entities) from and to the membrane orders of magnitude faster than molecular diffusion, like a conveyer belt. As a result, this system would not require such a high surface area as found in natural lungs, eventually eliminating many complex issues of scale-up fabrication and integration encountered in natural lung mimicking. Furthermore, the decreased surface area would minimize inflammatory response to the foreign surface and eventually clotting. This project will focus on proving the proposed concept of AM via in vitro blood flow testing. Detailed task plans are (1) design and optimize active membranes along with CFD (computational fluid dynamics) analysis; (2) microfabricate optimized AMs and integrate them in flow loops; and (3) in vitro evaluate gas exchange performance in the water/blood flow loops with hemocompatibility study. The primary innovation of this project is to develop a new class of AMs to replace existing diffusion-based transport mechanism in artificial lung. The significance of this work is to make a quantum leap in gas exchange that allows for truly portable (wearable), highly efficient, artificial lungs.